Cranberries are well known for their antioxidative, anti-inflammatory, antimicrobial, and anti-biofilm formation properties. Many studies indicate their potential for cancer prevention, blood sugar regulation, gastrointestinal and cardiovascular health, and antiviral properties. Such wide therapeutic potential for human health has made cranberries favourable for dietary formulations. Considering how prone patients are to accept treatment via nature's pharmacy instead of the conventional one, cranberries in the form of juice, tablets, capsules, or extracts are often prescribed alongside antibiotic therapy for urinary tract infection (UTI) treatment. This review paper aims to provide a better understanding of the limitations of the usage of berry dietary formulations for health improvement. The healing potential of cranberries is limited due to the bioaccessibility of their ingredients and their pharmacokinetic properties. Although rich with pharmacologically active substances, including anthocyanins, proanthocyanidins, vitamin C, vitamins (B1, B2, B3, B5, B6, B9), and organic acids, their potential is limited due to low absorption and distribution, extensive metabolism, and elimination. The variability in gene expression affecting the biosynthesis of anthocyanins and proanthocyanidins within the Vaccinium berries results in diminished concentrations of active ingredients within the plant material itself. Also, the results from the clinical trials are inconsistently standardized. This paper offers a comprehensive analysis of the available data and presents a clear direction for future research.

Introduction: Cranberry (Vaccinium macrocarpon) and Vitamin D have both demonstrated significant potential in combating microbial infections, particularly in the oral environment. Cranberry is known for its bioactive compounds, such as proanthocyanidins, flavonoids and organic acids, which exhibit antibacterial properties, while Vitamin D plays a crucial role in bone metabolism and immune response. This study aims to evaluate the antimicrobial efficacy of dental implants coated with cranberry extract and Vitamin D to inhibit bacterial biofilm formation and improve osseointegration. 

Materials and Methods: Titanium dental implants were coated with a cranberry hydrogel solution containing Vitamin D. The process involved surface preparation, dip coating and curing of the implants. Sub-gingival plaque samples were collected from patients with peri-implantitis for microbial analysis. In vitro biofilm formation was assessed on both coated and uncoated implants, followed by a colony reduction ability assessment where biofilm from the implant surfaces was dislodged and cultured to quantify bacterial colony-forming units (CFUs). 

Results: The results indicated a significant reduction in bacterial colonies in the test group (coated implants) compared to the control group (uncoated implants). The cranberry/Vitamin D coating effectively inhibited the growth of black-pigmented microbes. The test group showed a notable decrease in CFU count, confirming the antimicrobial properties of the coating. 

Conclusion: Cranberry and Vitamin D-coated dental implants exhibit significant antimicrobial activity, reducing bacterial colonisation and promoting better clinical outcomes in terms of infection control and bone healing. The use of natural bioactive compounds on implant surfaces represents a viable option to enhance the success rate of dental implants. However, further clinical trials are needed to validate long-term efficacy.

Background: High prevalence of urinary tract infections (UTI), including cystitis, and concern for antimicrobial resistance justify safe and effective nonantibiotic therapies for prevention of recurrent UTI (rUTI). Objectives: This study investigated the effect of a whole cranberry fruit powder supplement on incidence of culture-confirmed UTI (primary outcome) in females with rUTI history.

Methods: This multicenter, 6-mo, randomized, placebo-controlled, double-blind study enrolled 150 healthy females [18-65 y, body mass index (BMI) >17.5 and <35 kg/m2] with rUTI defined as >=3 UTIs in the last year or <=2 UTIs in the last 6 mo, excluding those with >5 UTIs in the last 6 mo. Participants consumed either 1 capsule of 500 mg/d of whole cranberry powder (Pacran) or placebo. Culture-confirmed UTIs (>108cfu/L) were assessed throughout the intervention period at unscheduled clinic visits whenever participants experienced UTI symptoms and at baseline, 3- and 6-mo clinic visits. Symptomatic suspected UTIs were defined as participant-reported UTI-associated symptoms at unscheduled visits. 

Results: Whole cranberry powder capsules reduced culture-confirmed UTI risk compared with placebo by 52% (adjusted relative risk [RR]: 0.48; 95% confidence interval [CI]: 0.26, 0.87; P = 0.01); reduced Escherichia coli UTIs (RR: 0.49; 95% CI: 0.24, 1.01; P = 0.05); reduced incidence of UTI with urinary frequency and urgency symptomatology (RR: 0.29; 95% CI:0.13, 0.63; P < 0.01); delayed time to first UTI episode (adjusted hazard ratio [HR]: 0.36; 95% CI: 0.18, 0.74; P = 0.01); and reduced the mean total number of UTIs per participant (adjusted incidence rate ratio IRR: 0.41; 95% CI: 0.21, 0.79; P = 0.01). Significant differences between groups in incidence of symptomatic suspected UTIs and culture-confirmed dysuria were not observed. Exploratory scores for UTI-related female sexual matters, assessed in a subset of sexually active, consenting females, did not differ significantly between groups. No safety concerns were reported. 

Conclusion: This study shows that whole cranberry powder capsules do not impact safety markers and reduce the incidence of culture-confirmed UTI and several other UTI-related outcomes in healthy females with rUTI history. This trial was registered at clinicaltrials.gov asNCT03042273.

This study aimed to determine whether a polyphenol-rich cranberry beverage affects skin properties, lipids, and the microbiome in women using a randomized, double-blinded, placebo-controlled, cross-over design. Twenty-two women with Fitzpatrick skin types 2-3 were randomized to drink a cranberry beverage or placebo for six weeks. After a 21-day washout, they consumed the opposite beverage for six weeks. Six weeks of cranberry beverage significantly reduced UVB-induced erythema, improved net elasticity on the face and forearm, smoothness on the face, and gross elasticity on the forearm compared to the placebo. When stratified by age, these effects of the cranberry beverage were primarily observed in women >40 years old. SOD activities were improved after six weeks of cranberry beverage consumption compared to the placebo, while glutathione peroxide and TNF- alpha were improved compared to baseline. These effects were found to differ by age group. Skin lipid composition was modulated by both the cranberry beverage and the placebo. Cranberry beverages did not change alpha - or beta -diversity but altered the abundance of several skin microbes at the species and strain level. Consumption of a cranberry beverage for six weeks improved specific skin properties and oxidative stress and modulated skin lipids and microbiome compared to placebo.

Objectives: This study examined the effect of a 4-week unsweetened cranberry beverage (CRAN) (317 mg polyphenols) versus placebo beverage (PLAC) ingestion (240 mL/day) on moderating exercise-induced changes in innate immunity. 

Methods: Participants included 25 male and female non-elite cyclists. A randomized, placebo-controlled, double-blind crossover design was used with two 4-week supplementation periods and a 2-week washout period. Supplementation periods were followed by an intensive 2.25 h cycling bout. Six blood samples were collected before and after supplementation (in an overnight fasted state) and at 0 h, 1.5 h, 3 h, and 24 h post-exercise. Stool and urine samples were collected pre- and post-supplementation. Outcome measures included serum creatine kinase, myoglobin, and cortisol, complete blood counts, plasma untargeted proteomics, plasma-targeted oxylipins, untargeted urine metabolomics, and stool microbiome composition via whole genome shotgun (WGS) sequencing. 

Results: Urine CRAN-linked metabolites increased significantly after supplementation, but no trial differences in alpha or beta microbiota diversity were found in the stool samples. The 2.25 h cycling bout caused significant increases in plasma arachidonic acid (ARA) and 53 oxylipins (FDR q-value < 0.05). The patterns of increase for ARA, four oxylipins generated from ARA-cytochrome P-450 (CYP) (5,6-, 8,9-, 11,12-, and 14,15-diHETrEs), two oxylipins from linoleic acid (LA) and CYP (9,10-DiHOME, 12,13-DiHOME), and two oxylipins generated from LA and lipoxygenase (LOX) (9-HODE, 13-HODE) were slightly but significantly higher for the CRAN versus PLAC trial (all interaction effects, p < 0.05). The untargeted proteomics analysis showed that two protein clusters differed significantly between the CRAN and PLAC trials, with CRAN-related elevations in proteins related to innate immune activation and reduced levels of proteins related to the regulation of the complement cascade, platelet activation, and binding and uptake of ligands by scavenger receptors. No trial differences were found for cortisol and muscle damage biomarkers. 

Conclusion: CRAN versus PLAC juice resulted in a significant increase in CRAN-related metabolites but no differences in the gut microbiome. CRAN supplementation was associated with a transient and modest but significant post-exercise elevation in selected oxylipins and proteins associated with the innate immune system.

BACKGROUND/AIMS: Phenobarbital (PB), commonly used for epilepsy management, is associated with testicular dysfunction after prolonged use. This study aimed to evaluate the ameliorative effects of cranberry (CB) and vitamin C (Vit-C) on PB-induced reproductive toxicity in rats. 

METHODS: Forty male Wistar rats were divided into five groups. G1 was the negative control, while G2 received PB (160 mg/kg orally) for one month. Groups G3 and G4 received PB followed by CB (500 mg/kg) and Vit-C (27 mg/kg) treatments, respectively. G5 received PB followed by a combined CB and Vit-C regimen. The levels of catalase (CAT), superoxide dismutase (SOD), glutathione reduced (GSH), and malondialdehyde (MDA) were determined using standard biochemical assays. Histological changes in testicular tissues were assessed, and caspase-3 expression was quantified via immunohistochemistry. 

RESULTS: PB exposure increased MDA levels, reduced SOD and CAT activity, and disrupted testicular histology, with elevated caspase-3 expression indicating heightened apoptosis. Treatment with CB or Vit-C significantly restored antioxidant enzyme activities, reduced MDA levels, and ameliorated histological abnormalities. Co-treatment with CB and Vit-C yielded the most pronounced protective effects, including reduced caspase-3 expression and improved testicular structure. 

CONCLUSION: CB and Vit-C demonstrate significant protective effects against PB-induced testicular toxicity, likely due to their antioxidative and anti-apoptotic properties. Co-administration of these agents offers an effective strategy to mitigate reproductive toxicities associated with prolonged PB use. © Copyright by the Author(s). Published by Cell Physiol Biochem Press.

Nephrolithiasis is a common disease and incurs a significant burden on the health care system globally. Patients with kidney stones can be treated with natural remedy such as cranberry, pomegranate, and grape juice. Patients with kidney stone experience anxiety and insomnia as a result of the pain caused by the stones. As a result, physicians may prescribe anxiolytics to treat anxiety, among which alprazolam is a commonly prescribed medication. Meanwhile, cranberry and pomegranate juice are prescribed by many herbal specialists for the treatment of renal calculi. The enzyme CYP3A4 primarily metabolizes alprazolam, while fruit juices such as cranberry and pomegranate juices are potent inhibitors of CYP3A4. Therefore, there could be a drug-food interaction between alprazolam and cranberry and pomegranate juices when consumed concomitantly. A detailed pharmacodynamic and pharmacokinetic investigation is required to ascertain the food-drug interaction between alprazolam, cranberry, and pomegranate juice to avoid the possible toxicity of alprazolam. This review article provides insights about the possible CYP3A4-associated drug interactions between alprazolam and juices of cranberry and pomegranate, for the safe and effective usage of alprazolam in treating anxiety disorders caused by kidney stones.

Cranberry-derived proanthocyanidin (PAC) is processed by the gut microbiota to produce 3-(4-hydroxyphenyl)-propionic acid (HPPA), among other metabolites. These data are in support of the article entitled, "Cranberry proanthocyanidin and its microbial metabolite 3,4-dihydroxyphenylacetic acid, but not 3-(4-hydroxyphenyl)-propionic acid, partially reverse pro-inflammatory microRNA responses in human intestinal epithelial cells," published in Molecular Nutrition and Food Research [1]. Here we describe data generated by nCounterR Human v3 miRNA Expression Panel of RNA obtained from Caco-2BBe1 cells exposed to two different concentrations of cranberry extract rich in PAC (50 micro g/ml or 100 micro g/ml) or 3-(4-hydroxyphenyl)-propionic acid (5 micro g/ml or 10 micro g/ml) for 24 h, then stimulated with 1 ng/ml of IL-1 beta or not (mock) for three hours. The raw data are publicly available at the NCBI GEO database GSE237078. This work also includes descriptive methodological procedures, treatment-responsive microRNA (miRNA) expression profiles in Caco-2BBe1 cells, and in silico mRNA gene target and pathway enrichment analyses of significantly differentially expressed miRNAs (q < 0.001). Cranberry and its components have recognized health benefits, particularly in relation to combatting inflammation and pathogenic bacterial adhesion. These data will be valuable as a reference to study the response of intestinal cells to other polyphenol-rich food sources, analyze gut microbial responses to cranberry and its metabolites in different cell lines and mammalian hosts to elucidate individualized effects, and to delineate the role of the gut microbiota in facilitating the benefits of cranberry. Moreover, these data will aid in expanding our knowledge on the mechanisms underlying the benefits of cranberry and its components.

Background: The aim of this double-blind randomized placebo-controlled clinical trial was to evaluate the efficacy of a multinutrient supplement as an add-on therapy to scaling and root planing for patients with periodontitis. 

Methods: Forty-two patients with stage III or IV periodontitis were randomly allocated to a 2-month treatment of either a multinutrient supplement containing vitamin C, vitamin E, zinc, selenium, alpha-lipoic-acid, cranberry extract, grapeseed extract, and coenzyme Q10 or placebo capsules as an adjunct to conservative periodontal therapy. Periodontal parameters, including probing pocket depth, gingival recession, bleeding on probing, approximal plaque index, and papillary bleeding index, were assessed. Clinical attachment loss, periodontal inflamed surface area, periodontal epithelial surface area, and percentages of pocket sites with <=3, <=4, >=5, >=6, >=7, and >=4 mm with bleeding on probing were calculated. 

Results: All clinical parameters significantly improved from baseline to reevaluation within each group (p < 0.05). Multinutrient intake resulted in a significantly higher reduction of probing-pocket-depth (-0.75 +or- 0.42 mm) and bleeding-on-probing (-21.9 +or- 16.1%) from baseline to reevaluation compared with placebo (-0.51 +or- 0.30 mm, p = 0.040 and -12.5 +or- 9.8%, p = 0.046, respectively). All periodontal parameters showed insignificantly higher improvements in patients receiving the supplement compared with those receiving the placebo (p > 0.05). 

Conclusion: Multinutrient supplementation as an adjunct to nonsurgical treatment of periodontitis showed some additional benefit regarding probing-pocket-depth and bleeding-on-probing. However, the clinical relevance needs to be further explored.

A promising approach for managing root caries is the use of cross-linking agents to stabilize collagen. However, despite testing various natural and synthetic agents in vitro, their efficacy remains uncertain. The aim of this review was to examine which cross-linking agent performs better in reducing root caries lesion depth and the release of hydroxyproline, which is a marker of collagen degradation. Studies evaluating the impact of cross-linking agents on dentin were included, while studies performed on enamel surface/cell cultures and studies evaluating collagenase inhibitors were excluded, among others. A comprehensive search covered eight databases, and study quality was assessed using the QUINN Tool for in vitro dental studies. Synthesis of the results was done using a Bayesian network meta-analysis to compare agents. Fifty studies involving 31 cross-linking agents were included for qualitative synthesis. The network meta-analysis for lesion depth involved 284 samples across 36 comparisons and ranked cross-linking agents in terms of their caries lesion depth-reducing effect (from best to worst): naringin > quercetin > riboflavin > proanthocyanidins > hesperidin > glutaraldehyde > cranberry > grape seed extract > untreated controls. Only naringin, quercetin, proanthocyanidins, and glutaraldehyde showed statistically significant efficacy over untreated controls. Cranberry extract excelled in reducing hydroxyproline release, followed by proanthocyanidins. In conclusion, proanthocyanidins positively affected both outcomes, suggesting they are prime candidates for translational research. Clinical studies are now essential to evaluate their real-world effectiveness against root caries. PROSPERO-CRD42023404911. Copyright © 2024 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.